Indolylalkylidenehydrazine-carboximidamide derivatives as 5-hydroxytryptamine-6 ligands

ABSTRACT

The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of a disorder relating to or affected by the 5-HT6 receptor.

This application claims priority from copending provisional applicationSer. No. 60/379,479, filed May 10, 2002, the entire disclosure of whichis hereby incorporated by reference.

BACKGROUND OF THE INVENTION

Various central nervous system disorders such as anxiety, depression,motor disorders, etc., are believed to involve a disturbance of theneurotransmitter 5-hydroxytryptamine (5-HT) or serotonin. Serotonin islocalized in the central and peripheral nervous systems and is known toaffect many types of conditions including psychiatric disorders, motoractivity, feeding behavior, sexual activity, and neuroendocrineregulation among others. The effects of serotonin are regulated by thevarious 5-HT receptor subtypes. Known 5-HT receptors include the 5-HT1family (e.g. 5-HT1A), the 5-HT2 family (e.g. 5-HT2A), 5-HT3, 5-HT4,5-HT5, 5-HT6 and 5-HT7 subtypes.

The recently identified human 5-hydroxytryptamine-6 (5-HT6) receptorsubtype has been cloned, and the extensive distribution of its mRNA hasbeen reported. Highest levels of 5-HT6 receptor mRNA have been observedin the olfactory tubercle, the striatum, nucleus accumbens, dentategyrus and CA1, CA2 and CA3 regions of the hippocampus. Lower levels of5-HT6 receptor mRNA are seen in the granular layer of the cerebellum,several diencephalic nuclei, amygdala and in the cortex. Northern blotshave revealed that 5-HT6 receptor mRNA appears to be exclusively presentin the brain, with little evidence for its presence in peripheraltissues. The high affinity of a number of antipsychotic agents for the5-HT6 receptor, in addition to its mRNA localization in striatum,olfactory tubercle and nucleus accumbens suggests that some of theclinical actions of these compounds may be mediated through thisreceptor. Therefore, 5-HT6 receptor ligands are believed to be ofpotential use in the treatment of certain CNS disorders such as anxiety,depression, epilepsy, obsessive compulsive disorder, attention deficitdisorder, migraine, cognitive memory enhancement (e.g. for the treatmentof Alzheimer's disease), sleep disorders, feeding disorders (e.g.anorexia or bulimia), neurodegenerative disorders (e.g. stroke or headtrauma), panic attacks, withdrawal from drug abuse (e.g. cocaine,ethanol, nicotine or benzodiazepines), schizophrenia, or the like; or inthe treatment of certain gastrointestinal disorders such as irritablebowel syndrome.

Therefore, it is an object of this invention to provide compounds whichare useful as therapeutic agents in the treatment of a variety ofcentral nervous system disorders related to or affected by the 5-HT6receptor.

It is another object of this invention to provide therapeutic methodsand pharmaceutical compositions useful for the treatment of centralnervous system disorders related to or affected by the 5-HT6 receptor.

It is a feature of this invention that the compounds provided may alsobe used to further study and elucidate the 5-HT6 receptor.

These and other objects and features of the invention will become moreapparent by the detailed description set forth hereinbelow.

SUMMARY OF THE INVENTION

The present invention provides anindolylalkylidenehydrazinecarboximidamide compound of formula I

wherein

-   -   X is N or CR₃;    -   Y is N or CR₄;    -   Q is SO₂, CO, CO₂, CONR₁₁ or CSNR₁₂;    -   R₁, R₂, R₃ and R₄ are each independently H, halogen, CN,        OCO₂R₁₃, CO₂ R₁₄, CONR₁₅R₁₆, NR₁₇SO₂R₁₈, NR₁₉COR₂₈, SO_(n)R₂₀,        NR₂₁R₂₂, OR₂₃, COR₂₄ or a C₁-C₆alkyl, C₂-C₆alkenyl,        C₂-C₆alkynyl, C₃-C₆cycloalkyl, cycloheteroalkyl, aryl or        heteroaryl group each optionally substituted;    -   R₅, R₆ and R₇ are each independently H or a C₁-C₆alkyl,        C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₁₂cycloalkyl, cycloheteroalkyl,        aryl or heteroaryl group each optionally substituted or R₅ and        R₆ maybe taken together with the atoms to which they are        attached to form an optionally substituted 5- to 7-membered        ring;    -   R₈ is H or a C₁-C₆alkyl or C₃-C₁₀cycloalkyl group each        optionally substituted;    -   R₉ is H, halogen, CN, NO₂, NR₂₅R₂₆, OR₂₇ or a C₁-C₆alkyl, aryl        or heteroaryl group each optionally substituted or R₈ and R₉ may        be taken together with the atoms to which they are attached to        form an optionally substituted 5- to 7-membered ring optionally        containing one or two heteroatoms selected from O, N or S;    -   R₁₀ is a C₁-C₆alkyl, aryl or heteroaryl group each optionally        substituted or an optionally substituted 8- to 13-membered        bicyclic or tricyclic ring system having a N atom at the        bridgehead and optionally containing 1, 2 or 3 additional        heteroatoms selected from N, O or S with the proviso that when        R₈ is H or C₁-C₆alkyl and Q is CO then R₁₀ must be other than        C₁-C₆alkyl or aryl;    -   n is 0 or an integer of 1 or 2;    -   R₁₁ and R₁₂ are each independently H or a C₁-C₆alkyl, aryl or        heteroaryl group each optionally substituted;    -   R₁₃, R₁₄, R₁₈, R₂₀, R₂₃, R₂₄, R₂₇ and R₂₈ are each independently        H or a C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl,        cycloheteroalkyl, aryl or heteroaryl group each optionally        substituted;    -   R₁₅ and R₁₆ are each independently H or an optionally        substituted C₁-C₆alkyl group; and    -   R₁₇, R₁₉, R₂₁, R₂₂, R₂₅ and R₂₆ are each independently H or an        optionally substituted C₁-C₄alkyl group or R₂₁, and R₂₂ may be        taken together with the atom to which they are attached to form        a 5- to 7-membered ring optionally containing another heteroatom        selected from O, N or S; or        the stereoisomers thereof, the tautomers thereof or the        pharmaceutically acceptable salts thereof.

The present invention also provides methods and compositions useful forthe therapeutic treatment of central nervous system disorders related toor affected by the 5-HT6 receptor.

DETAILED DESCRIPTION OF THE INVENTION

The 5-hydroxytryptamine-6 (5-HT6) receptor is one of the most recentreceptors to be identified by molecular cloning. Its ability to bind awide range of therapeutic compounds used in psychiatry, coupled with itsintriguing distribution in the brain has stimulated significant interestin new compounds which are capable of interacting with or affecting saidreceptor. Significant efforts are being made to understand the possiblerole of the 5-HT6 receptor in psychiatry, cognitive dysfunction, motorfunction and control, memory, mood and the like. To that end, compoundswhich demonstrate a binding affinity for the 5-HT6 receptor areearnestly sought both as an aid in the study of the 5-HT6 receptor andas potential therapeutic agents in the treatment of central nervoussystem disorders, for example see C. Reavill and D. C. Rogers, CurrentOpinion in Investigational Drugs, 2001, 2(1):104-109, Pharma Press Ltd.

Surprisingly, it has now been found thatindolylalkylidenehydralzinecarboximidamide derivatives of formula Idemonstrate 5-HT6 affinity. Advantageously, said amide derivatives maybe used as effective therapeutic agents for the treatment of centralnervous system (CNS) disorders associated with or affected by the 5-HT6receptor. Accordingly, the present invention providesindolylalkylidenehydrazinecarboximidamide derivatives of formula I.

wherein

-   -   X is N or CR₃;    -   Y is N or CR₄;    -   Q is SO₂, CO, CO₂, CONR₁₁ or CSNR₁₂;    -   R₁, R₂, R₃ and R₄ are each independently H, halogen, CN,        OCO₂R₁₃, CO₂ R₁₄, CONR₁₅R₁₆, NR₁₇SO₂R₁₈, NR₁₉COR₂₈, SO_(n)R₂₀,        NR₂₁R₂₂, OR₂₃, COR₂₄ or a C₁-C₆alkyl, C₂-C₆alkenyl,        C₂-C₆alkynyl, C₃-C₆cycloalkyl, cycloheteroalkyl, aryl or        heteroaryl group each optionally substituted;    -   R₅, R₆ and R₇ are each independently H or a C₁-C₆alkyl,        C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₁₂Cycloalkyl, cycloheteroalkyl,        aryl or heteroaryl group each optionally substituted or R₅ and        R₆ maybe taken together with the atoms to which they are        attached to form an optionally substituted 5- to 7-membered        ring;    -   R₈ is H or a C₁-C₆alkyl or C₃-C₁₀cycloalkyl group each        optionally substituted; R₉ is H, halogen, CN, NO₂, NR₂₅R₂₆, OR₂₇        or a C₁-C₆alkyl, aryl or heteroaryl group each optionally        substituted or R₈ and R₉ may be taken together with the atoms to        which they are attached to form an optionally substituted 5- to        7-membered ring optionally containing one or two heteroatoms        selected from O, N or S;    -   R₁₀ is a C₁-C₆alkyl, aryl or heteroaryl group each optionally        substituted or an optionally substituted 8- to 13-membered        bicyclic or tricyclic ring system having a N atom at the        bridgehead and optionally containing 1, 2 or 3 additional        heteroatoms selected from N, O or S with the proviso that when        R₈ is H or C₁-C₆alkyl and Q is CO then R₁₀,must be other than        C₁-C₆alkyl or aryl;    -   n is 0 or an integer of 1 or 2;    -   R₁₁ and R₁₂ are each independently H or a C₁-C₆alkyl, aryl or        heteroaryl group each optionally substituted;    -   R₁₃, R₁₄, R₁₈, R₂₀, R₂₃, R₂₄, R₂₇ and R₂₈ are each independently        H or a C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl,        cycloheteroalkyl, aryl or heteroaryl group each optionally        substituted;    -   R₁₅ and R₁₆ are each independently H or an optionally        substituted C₁-C₆alkyl group; and

R₁₇, R₁₉, R₂₁, R₂₂, R₂₅ and R₂₆ are each independently H or anoptionally substituted C₁-C₄alkyl group or R₂₁, and R₂₂ may be takentogether with the atom to which they are attached to form a 5- to7-membered ring optionally containing another heteroatom selected fromO, N or S; or

the stereoisomers thereof, the tautomers thereof or the pharmaceuticallyacceptable salts thereof.

As used in the specification and claims, the term halogen designates Br,Cl, I or F and the term cycloheteroalkyl designates a C₅-C₇cycloalkylring system containing 1 or 2 heteroatoms, which may be the same ordifferent, selected from N, O or S and optionally containing one doublebond. Exemplary of the cycloheteroalkyl ring systems included in theterm as designated herein are the following rings wherein W is NR, O orS; and R is H or an optional substituent as described hereinbelow:

Similarly, as used in the specification and claims, the term heteroaryldesignates a C₅-C₁₀ aromatic ring system containing 1, 2 or 3heteroatoms, which may be the same or different, selected from N, O orS. Such heteroaryl ring systems include pyrrolyl, azolyl, oxazolyl,thiazolyl, imidazolyl, furyl, thienyl, quinolinyl, isoquinolinyl,indolinyl, benzothienyl, benzofuranyl, benzisoxazolyl or the like. Theterm aryl designates carbocyclic aromatic ring systems such as phenyl,naphthyl, or the like. The term haloalkyl as used herein designates aC_(n)H_(2n+1) group having from one to 2n+1 halogen atoms which may bethe same or different and the term haloalkoxy as used herein designatesan OC_(n)H_(2n+1) group having from one to 2n+1 halogen atoms which maybe the same or different.

Exemplary of the 8- to 13-membered bicyclic or tricyclic ring systemshaving a N atom at the bridgehead and optionally containing 1, 2 or 3additional heteroatoms selected from N, O or S included in the term asdesignated herein are the following ring systems wherein W₂ is NR, O orS; and R is H or an optional substituent as described hereinbelow:

In the specification and claims, when the terms C₁-C₆alkyl,C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₇cycloalkyl, cycloheteroalkyl, aryl,heteroaryl or 8- to 13-membered bicyclic or tricyclic ring system havinga N atom at the bridgehead are designated as being optionallysubstituted, the substituent groups which are optionally present may beone or more of those customarily employed in the development ofpharmaceutical compounds or the modification of such compounds toinfluence their structure/activity, persistence, absorption, stabilityor other beneficial property. Specific examples of such substituentsinclude halogen atoms, nitro, cyano, thiocyanato, cyanato, hydroxyl,alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino,formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsulfinyl,alkylsulfonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl,benzyloxy, cycloheteroalkyl or cycloalkyl groups, preferably halogenatoms or lower alkyl groups. Typically, 0-3 substituents may be present.When any of the foregoing substituents represents or contains an alkylsubstituent group, this may be linear or branched and may contain up to12, preferably up to 6, more preferably up to 4 carbon atoms.

Pharmaceutically acceptable salts may be any acid addition salt formedby a compound of formula I and a pharmaceutically acceptable acid suchas phosphoric, sulfuric, hydrochloric, hydrobromic, citric, maleic,malonic, mandelic, succinic, fumaric, acetic, lactic, nitric, sulfonic,p-toluene sulfonic, methane sulfonic acid or the like.

Compounds of the invention include esters, carbamates or otherconventional prodrug forms, which in general, are functional derivativesof the compounds of the invention and which are readily converted to theinventive active moiety in vivo. Correspondingly, the method of theinvention embraces the treatment of the various conditions describedhereinabove with a compound of formula I or with a compound which is notspecifically disclosed but which, upon administration, converts to acompound of formula I in vivo. Also included are metabolites of thecompounds of the present invention defined as active species producedupon introduction of these compounds into a biological system.

Compounds of the invention may exist as one or more stereoisomers. Thevarious stereoisomers include enantiomers, diastereomers, atropisomersand geometric isomers. One skilled in the art will appreciate that onestereoisomer may be more active or may exhibit beneficial effects whenenriched relative to the other stereoisomer(s) or when separated fromthe other stereoisomer(s). Additionally, the skilled artisan knows howto separate, enrich or selectively prepare said stereoisomers.Accordingly, the present invention comprises compounds of formula I, thestereoisomers thereof, the tautomers thereof and the pharmaceuticallyacceptable salts thereof. The compounds of the invention may be presentas a mixture of stereoisomers, individual stereoisomers, or as anoptically active or enantiomerically pure form.

Preferred compounds of the invention are those compounds of formula Iwherein Q is SO₂. Also preferred are those compounds of formula Iwherein R₁₀ is an aryl or heteroaryl group each optionally substitutedor an optionally substituted 8- to 13-member bicyclic or tricyclic ringsystem having a N atom at the bridgehead and optionally containing 1, 2or 3 additional heteroatoms selected from N, O or S. Another group ofpreferred compounds of formula I are those compounds wherein X is CR₃and Y is CR₄.

More preferred compounds of the invention are those compounds of formulaI wherein Q is SO₂ and R₉ is H. Another group of more preferredcompounds are those compounds of formula I wherein Q is SO₂; X is CR₃; Yis CR₄; and R₉ is H. Further more preferred compounds are those formulaI compounds wherein Q is SO₂; X is CR₃; Y is CR₄; R₉ is H; and R₁₀ is anaryl or heteroaryl group each optionally substituted or an optionallysubstituted 8- to 15-member bicyclic or tricyclic ring system having a Natom at the bridgehead optionally containing 1, 2 or 3 additionalheteroatoms selected from N, O or S.

Exemplary of the compounds of the invention are:

-   1-[(4-methylphenyl)sulfonyl]-1H-indole-3-carbaldehyde    1,4,5,6-tetrahydropyrimidin-2-ylhydrazone,-   2-({1-[(4-methylphenyl)sulfonyl]-1H-indol-3-l}methylidene)hydrazinecarboximidamide,-   1-[(4-methylphenyl)sulfonyl]-1H-indole-3-carbaldehyde    4,5-dihydro-1H-imidazol-2-yl(methyl)hydrazone,-   2-{cyclohexyl[1-(phenylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide,-   2-{2-methyl-1-[1-(phenylsulfonyl)-1H-indol-3-yl]propylidene}hydrazinecarboximidamide,-   2-{2-phenyl-1-[1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{3-methyl-1-[1-(phenylsulfonyl)-1H-indol-3-yl]butylidene}hydrazinecarboximidamide,-   2-{(E,2E)-3-(2-chlorophenyl)-1-[1-(phenylsulfonyl)-1H-indol-3-yl]prop-2-enylidene}-hydrazinecarboximidamide,-   2-{1-[1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[5-chloro-2-methyl-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide-   2-{1-[2-(4-fluorophenyl)-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide-   2-{1-[2-(3-chloro-4-fluorophenyl)-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[2-(3,4-difluorophenyl)-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[2-(2-naphthyl)-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[2-phenyl-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[5-cyano-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[5-iodo-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[5-nitro-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[5-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{[5-methoxy-1-(phenylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide,-   2-{[5-(benzyloxy)-1-(phenylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide,-   2-(1-{1-[(2-amino-4-methyl-1,3-thiazol-5-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(4-aminophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-{1-[1-(2,1,3-benzothiadiazol-4-ylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[1-([1,1′-biphenyl]-4-ylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-(1-{1-[(4-bromo-2,5-dichlorothien-3-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(4-bromo-5-chlorothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(3-bromo-5-chlorothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(4-bromophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(2-bromophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(3-bromophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(5-bromothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(5-chloro-2-methoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(5-chlorothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-[1-(1-{[5-(dimethylamino)-1-naphthyl]sulfonyl}-1H-indol-3-yl)ethylidene]hydrazinecarboximidamide,-   2-(1-{1-[(4,5-dibromothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(2,5-dichlorophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(2,5-dichlorothien-3-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(4,5-dichlorothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(3,5-dimethylisoxazol-4-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(4-fluorophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-{1-[1-({5-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]thien-2-yl}sulfony)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-(1-{1-[(2-methyl-5-nitrophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(1-methyl-1H-imidazol-4-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-[1-(1-{[4-(methylsulfonyl)phenyl]sulfonyl}-1H-indol-3-yl)ethylidene]hydrazinecarboximidamide,-   2-{1-[1-({5-[2-(methylthio)pyrimidin-4-yl]thien-2-yl}sulfonyl)-1H-indol-3-yl]ethylidene}-hydrazinecarboximidamide,-   2-{1-[1-(1-naphthylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-(1-{1-[(2-nitrophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(4-nitrophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(5-pyridin-2-ylthien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-[1-(1-{[4-(trifluoromethoxy)phenyl]sulfonyl}-1H-indol-3-yl)ethylidene]hydrazinecarboximidamide,-   phenyl    3-(1-{2-[amino(imino)methyl]hydrazono}ethyl)-1H-indole-1-carboxylate,-   3-(1-{2-[amino(imino)methyl]hydrazono}ethyl)-N-phenyl-1H-indole-1-carboxamide,-   2-[1-(1-benzoyl-1H-indol-3-yl)ethylidene]hydrazinecarboximidamide,-   2-{1-[1-(methylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[1-(methylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-{cyclopropyl[1-(methylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide,-   2-{1-[1-(butylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[1-(butylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-[[1-(butylsulfonyl)-1H-indol-3-yl](cyclopropyl)methylidene]hydrazinecarboximidamide,-   2-(1-{1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}pentylidene)hydrazinecarboximidamide,-   2-(cyclopropyl{1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}methylidene)hydrazinecarboximidamide,-   2-{1-[1-(2-naphthylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[1-(2-naphthylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-{cyclopropyl[1-(2-naphthylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide,-   2-{1-[1-(phenylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-{cyclopropyl[1-(phenylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide,-   2-(1-{1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}pentylidene)hydrazinecarboximidamide,-   2-(cyclopropyl{1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}methylidene)hydrazinecarboximidamide,-   2-{1-[5-chloro-1-(methylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[5-chloro-1-(methylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-[[5-chloro-1-(methylsulfonyl)-1H-indol-3-yl](cyclopropyl)methylidene]hydrazinecarboximidamide,-   2-{1-[1-(butylsulfonyl)-5-chloro-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[1-(butylsulfonyl)-5-chloro-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-[[1-(butylsulfonyl)-5-chloro-1H-indol-3-yl](cyclopropyl)methylidene]hydrazinecarboximidamide,-   2-(1-{5-chloro-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide.-   2-(1-{5-chloro-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}pentylidene)hydrazinecarboximidamide,-   2-[{5-chloro-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}(cyclopropyl)methylidene]hydrazinecarboximidamide,-   2-{1-[5-chloro-1-(2-naphthylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[5-chloro-1-(2-naphthylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-[[5-chloro-1-(2-naphthylsulfonyl)-1H-indol-3-yl](cyclopropyl)methylidene]hydrazinecarboximidamide,-   2-{1-[5-chloro-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[5-chloro-1-(phenylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-[[5-chloro-1-(phenylsulfonyl)-1H-indol-3-yl](cyclopropyl)methylidene]hydrazinecarboximidamide,-   2-(1-{5-chloro-1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{5-chloro-1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}pentylidene)hydrazinecarboximidamide,-   2-[{5-chloro-1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}(cyclopropyl)-methylidene]hydrazinecarboximidamide,-   2-{1-[2-(4-chlorophenyl)-1-(methylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[2-(4-chlorophenyl)-1-(methylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-[[2-(4-chlorophenyl)-1-(methylsulfonyl)-1H-indol-3-yl](cyclopropyl)methylidene]hydrazinecarboximidamide,-   2-[{2-(4-chlorophenyl)-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}(cyclopropyl)-methylidene]hydrazinecarboximidamide,-   2-[[2-(4-chlorophenyl)-1-(2-naphthylsulfonyl)-1H-indol-3-yl](cyclopropyl)methylidene]hydrazinecarboximidamide,-   2-{1-[2-(4-chlorophenyl)-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[2-(4-chlorophenyl)-1-(phenylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-[[2-(4-chlorophenyl)-1-(phenylsulfonyl)-1H-indol-3-yl](cyclopropyl)methylidene]hydrazinecarboximidamide,-   2-(1-{2-(4-chlorophenyl)-1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-[{2-(4-chlorophenyl)-1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}(cyclopropyl)-methylidene]hydrazinecarboximidamide,-   2-{1-[6-fluoro-1-(methylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[6-fluoro-1-(methylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-{cyclopropyl[6-fluoro-1-(methylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide,-   2-{1-[1-(butylsulfonyl)-6-fluoro-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[1-(butylsulfonyl)-6-fluoro-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-[[1-(butylsulfonyl)-6-fluoro-1H-indol-3-yl](cyclopropyl)methylidene]hydrazinecarboximidamide,-   2-(1-{6-fluoro-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{6-fluoro-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}pentylidene)hydrazinecarboximidamide,-   2-(cyclopropyl{6-fluoro-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}methylidene)hydrazinecarboximidamide,-   2-{1-[6-fluoro-1-(2-naphthylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[6-fluoro-1-(2-naphthylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-{cyclopropyl[6-fluoro-1-(2-naphthylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide,-   2-{1-[6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide,-   2-{cyclopropyl[6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide,-   2-(1-{1-[(3,4-dimethoxyphenyl)sulfonyl]-6-fluoro-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide,-   2-(1-{1-[(3,4-dimethoxyphenyl)sulfonyl]-6-fluoro-1H-indol-3-yl}pentylidene)hydrazinecarboximidamide,-   2-(cyclopropyl{1-[(3,4-dimethoxyphenyl)sulfonyl]-6-fluoro-1H-indol-3-yl}methylidene)hydrazinecarboximidamide,-   2-{1-[5-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl]propylidene}hydrazinecarboximidamide,-   2-(1-{1-[(4-aminophenyl)sulfonyl]-5-fluoro-1H-indol-3-yl}propylidene)hydrazinecarboximidamide,-   2-{1-[5-fluoro-1-(2-naphthylsulfonyl)-1H-indol-3-yl]propylidene}hydrazinecarboximidamide,-   2-(1-{1-[(4-aminophenyl)sulfonyl]-5-chloro-1H-indol-3-yl}propylidene)hydrazinecarboximidamide,-   2-{1-[5-chloro-1-(2-naphthylsulfonyl)-1H-indol-3-yl]propylidene}hydrazinecarboximidamide,-   N-pentyl-2-{1-[1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}-N-propylhydrazinecarboximidamide,-   N-benzyl-2-{1-[1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-{1-[1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}-N-(pyridin-2-ylmethyl)hydrazinecarboximidamide,-   N-(2-hydroxyethyl)-2-{1-[1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide,-   2-[6-chloro-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]-hydrazinecarboximidamide,-   2-[6-chloro-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one    4,5-dihydro-1H-imidazol-2-ylhydrazone,-   2-[6-chloro-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one    4,5-dihydro-1H-imidazol-2-yl(methyl)hydrazone,-   2-[9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]hydrazinecarboximidamide,-   2-[6-bromo-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one    4,5-dihydro-1H-imidazol-2-ylhydrazone,-   2-[6-bromo-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one    4,5-dihydro-1H-imidazol-2-yl(methyl)hydrazone,-   2-[6-bromo-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]hydrazinecarboximidamide,-   2-[6-chloro-9-(methylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]hydrazinecarboximidamide,-   2-{6-chloro-9-[(4-methoxyphenyl)sulfonyl]-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene}hydrazinecarboximidamide,-   2-{9-[(2-amino-4-methyl-1,3-thiazol-5-yl)sulfonyl]-6-chloro-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene}hydrazinecarboximidamide,-   2-[6-chloro-9-(2-naphthylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]hydrazinecarboximidamide,-   2-{6-chloro-9-[(3,4-dimethoxyphenyl)sulfonyl]-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene}hydrazinecarboximidamide,-   or the stereoisomers thereof, the tautomers thereof or the    pharmaceutically acceptable salts thereof.

Compounds of the invention may be prepared using conventional syntheticmethods and, if required, standard separation and isolation techniques.For example, compounds of formula I wherein Q is SO₂ and R₈ is H (Ia)may be prepared by reacting a compound of formula II withdimethylformamide (DMF) and phosporous oxychloride to give the3-carboxaldehyde of formula III, sulfonylating the formula III compoundwith the appropriate sulfonyl chloride, ClSO₂R₁₀, in the presence of abase such as NaH to give the sulfonylated compound of formula IV andreacting the formula IV compound with an aminoguanidine derivative offormula V to give the desired product of formula Ia. The reactionsequence is shown in flow diagram I.

Similarly, compounds of formula I wherein Q is SO₂ and R₈ is anoptionally substituted alkyl or cycloalkyl group (Ib) may be prepared byacylating a formula II compound with an acyl halide, R₈CO-Hal, to givethe 3-acyl compound of formula VI, sulfonylating the formula VIcompound, and reacting the sulfonylated product with an aminoguanidinederivative of formula V, as described in flow diagram II, to give thedesired formula Ib product. The reaction is shown in flow diagram IIwherein Hal represents Cl, Br or I.

Compounds of formula I wherein Q is SO₂ and R₈ and R₉ are taken togetherwith the atoms to which they are attached to form an optionallysubstituted six-membered ring (Ic) may be prepared by reacting1,3-cyclohexanedione with a hydrazine of formula VII to form thehydrazone of formula VIII, heating said formula VIII hydrazone in thepresence of trifluoroacetic acid (TFA) to form the 4-oxocarbazole offormula IX, and sequentially sulfonylating the formula IV compound andreacting the sulfonylated product with an aminoguanidine derivative asdescribed hereinabove to give the desired compound of formula Ic. Thereaction scheme is shown in flow diagram III.

Compounds of formula I wherein R₈ and R₉ are taken together to form a 5-or 7-membered ring (Id) may be prepared by the regioselective oxidationof a ring fused indole system as described by Oikawa et al,Heterocyclic, 1976, 4, 1959 and Comp. Het. Chem., 1984, 4, 253 to givethe intermediate of formula X which may be converted to the desiredformula (Id) product. The reaction scheme is shown in flow diagram IVwherein n is 1, 2 or 3.

Compounds of formula I wherein Q is CO, CO₂, CONR₁₁ or CSNR₁₂ may beprepared by reacting the intermediates of formulas III, VI, IX or X withthe appropriate acylhalide, α-haloester, isocyanate or isothiocyanate,respectively.

Azainodoles such as 4-azaindole or 7-azaindole may be prepared bymethods described in the literature, i.e., I. Mahadevan, I., Rasmussen,M., J. Het. Chem., 1992, 29, 359-367; Hands, D.; Bishop, B.; Cameron,M.; Edwards, J. S.; Cottrell, I. F.; Wright, S. H. B., Synthesis, 1996,877-882; Dobson, D.; Todd, A.; Gilmore, J., Synth. Commum. 1991, 21,611-167. In addition, azaindoles are also available commercially.

Sulfonyl chlorides, R₁₀SO₂Cl, may be obtained commercially or preparedby conventional techniques. For example,6-substituted-imidazo[2,1-b][1,3]thiazol-5-yl sulfonyl chlorides offormulas XIIIa and XIIIb may be prepared by reacting 2-amino-thiazolewith chloroacetic acid or a suitable chloromethyl ketone to give2-imino-4-thiazolin-3-ylacetic acid (XIa) or the2-imino-4-thiazolin-3-yl ketone (XIb), respectively; reacting either XIaor XIb with POCl₃ to give, in the case of XIa,6-chloroimidazo[2,1-b]thiazole (XIIa) or, in the case of XIb,6-substituted-imidazo[2,1-b]thiazole XIIb; and sequentially reacting therespective XIIa and XIIb compounds with chlorosulfonic acid and POCl₃ togive the desired sulfonyl chlorides of formulas XIIIa and XIIIb. Thereactions are illustrated in flow diagram V wherein R represents anoptional substituent as described hereinabove with the exclusion ofhalogen.

Advantageously, the present invention provides a process for thepreparation of a compound of formula I which comprises reacting acompound of formula XIV with an aminoguanidine derivative of formula Vin the presence of an acid, optionally in the presence of a solvent. Theprocess is shown in flow diagram VI.

Acids suitable for use in the process of the invention include acidssuch as HCl, HBr, H₂SO₄, HNO₂ or the like, preferably HCl. Solventssuitable for use in the process of invention include protic solventssuch as lower alkyl alcohols, i.e., methanol, ethanol, isopropanol,propanol or the like, preferably isopropanol.

Advantageously, the inventive compound of formula I may be utilized inthe treatment of central nervous system disorders relating to oraffected by the 5-HT6 receptor such as motor, mood, psychiatric,cognitive, neurodegenerative, or the like disorders, for example,Alzheimer's disease, Parkinson's disease, attention deficit disorder,anxiety, epilepsy, depression, obsessive compulsive disorder, migraine,sleep disorders, neurodegenerative disorders (such as head trauma orstroke), feeding disorders (such as anorexia or bulimia), schizophrenia,memory loss, disorders associated with withdrawal from drug or nicotineabuse, or the like or certain gastrointestinal disorders such asirritable bowel syndrome. Accordingly, the present invention provides amethod for the treatment of a disorder of the central nervous system(CNS) related to or affected by the 5-HT6 receptor in a patient in needthereof which comprises providing said patient a therapeuticallyeffective amount of a compound of formula I

wherein

-   -   X is N or CR₃;    -   Y is N or CR₄;    -   Q is SO₂, CO, CO₂, CONR or CSNR₁₂;    -   R₁, R₂, R₃ and R₄ are each independently H, halogen, CN,        OCO₂R₁₃, CO₂R₁₄, CONR₁₅R₁₆, NR₁₇SO₂R₁₈, NR₁₉COR₂₈, SO_(n)R₂₀,        NR₂₁R₂₂, OR₂₃, COR₂₄ or a C₁-C₆alkyl, C₂-C₆alkenyl,        C₂-C₆alkynyl, C₃-C₆cycloalkyl, cycloheteroalkyl, aryl or        heteroaryl group each optionally substituted;    -   R₅, R₆ and R₇ are each independently H or a C₁-C₆alkyl,        C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₁₂cycloalkyl, cycloheteroalkyl,        aryl or heteroaryl group each optionally substituted or R₅ and        R₆ maybe taken together with the atoms to which they are        attached to form an optionally substituted 5- to 7-membered        ring;    -   R₈ is H or a C₁-C₆alkyl or C₃-C₁₀cycloalkyl group each        optionally substituted;    -   R₉ is H, halogen, CN, NO₂, NR₂₅R₂₆, OR₂₇ or a C₁-C₆alkyl, aryl        or heteroaryl group each optionally substituted or R₈ and R₉ may        be taken together with the atoms to which they are attached to        form an optionally substituted 5- to 7-membered ring optionally        containing one or two heteroatoms selected from O, N or S;    -   R₁₀ is a C₁-C₆alkyl, aryl or heteroaryl group each optionally        substituted or an optionally substituted 8- to 13-membered        bicyclic or tricyclic ring system having a N atom at the        bridgehead and optionally containing 1, 2 or 3 additional        heteroatoms selected from N, O or S with the proviso that when        R₈ is H or C₁-C₆alkyl and Q is CO then R₁₀ must be other than        C₁-C₆alkyl or aryl;    -   n is 0 or an integer of 1 or 2;    -   R₁₁ and R₁₂ are each independently H or a C₁-C₆alkyl, aryl or        heteroaryl group each optionally substituted;    -   R₁₃, R₁₄, R₁₈, R₂₀, R₂₃, R₂₄, R₂₇ and R₂₈ are each independently        H or a C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl,        cycloheteroalkyl, aryl or heteroaryl group each optionally        substituted;    -   R₁₅ and R₁₆ are each independently H or an optionally        substituted C₁-C₆alkyl group; and

R₁₇, R₁₉, R₂₁, R₂₂, R₂₅ and R₂₆ are each independently H or anoptionally substituted C₁-C₄alkyl group or R₂₁ and R₂₂ may be takentogether with the atom to which they are attached to form a 5- to7-membered ring optionally containing another heteroatom selected fromO, N or S; or

the stereoisomers thereof, the tautomers thereof or the pharmaceuticallyacceptable salts thereof.

The term “providing” as used herein with respect to providing a compoundor substance covered by the invention, designates either directlyadministering such a compound or substance, or administering a prodrug,derivative or analog which forms an equivalent amount of the compound orsubstance within the body.

The compounds of formula I may be provided by oral or parenteraladministration or in any common manner known to be an effectiveadministration of a therapeutic agent to a patient in need thereof.

The therapeutically effective amount provided in the treatment of aspecific CNS disorder may vary according to the specific condition(s)being treated, the size, age and response pattern of the patient, theseverity of the disorder, the judgment of the attending physician andthe like. In general, effective amounts for daily oral administrationmay be about 0.01 to 1,000 mg/kg, preferably about 0.5 to 500 mg/kg andeffective amounts for parenteral administration may be about 0.1 to 100mg/kg, preferably about 0.5 to 50 mg/kg.

In actual practice, the compounds of the invention are provided byadministering the compound or a precursor thereof in a solid or liquidform, either neat or in combination with one or more conventionalpharmaceutical carriers or excipients. Accordingly, the presentinvention provides a pharmaceutical composition which comprises apharmaceutically acceptable carrier and an effective amount of acompound of formula I

wherein

-   -   X is N or CR₃;    -   Y is N or CR₄;    -   Q is SO₂, CO, CO₂, CONR₁₁ or CSNR₁₂;    -   R₁, R₂, R₃ and R₄ are each independently H, halogen, CN,        OCO₂R₁₃, CO₂R₁₄, CONR₁₅R₁₆, NR₁₇SO₂R₁₈, NR₁₉COR₂₈, SO_(n)R₂₀,        NR₂₁R₂₂, OR₂₃, COR₂₄ or a C₁-C₆alkyl, C₂-C₆alkenyl,        C₂-C₆alkynyl, C₃-C₆cycloalkyl, cycloheteroalkyl, aryl or        heteroaryl group each optionally substituted;    -   R₅, R₆ and R₇ are each independently H or a C₁-C₆alkyl,        C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₁₂cycloalkyl, cycloheteroalkyl,        aryl or heteroaryl group each optionally substituted or R₅ and        R₆ maybe taken together with the atoms to which they are        attached to form an optionally substituted 5- to 7-membered        ring;    -   R₈ is H or a C₁-C₆alkyl or C₃-C₁₀cycloalkyl group each        optionally substituted;    -   R₉ is H, halogen, CN, NO₂, NR₂₅R₂₆, OR₂₇ or a C₁-C₆alkyl, aryl        or heteroaryl group each optionally substituted or R₈ and R₉ may        be taken together with the atoms to which they are attached to        form an optionally substituted 5- to 7-membered ring optionally        containing one or two heteroatoms selected from O, N or S;    -   R₁₀ is a C₁-C₆alkyl, aryl or heteroaryl group each optionally        substituted or an optionally substituted 8- to 13-membered        bicyclic or tricyclic ring system having a N atom at the        bridgehead and optionally containing 1, 2 or 3 additional        heteroatoms selected from N, O or S with the proviso that when        R₈ is H or C₁-C₆alkyl and Q is CO then R₁₀ must be other than        C₁-C₆alkyl or aryl;    -   n is 0 or an integer of 1 or 2;    -   R₁₁ and R₁₂ are each independently H or a C₁-C₆alkyl, aryl or        heteroaryl group each optionally substituted;    -   R₁₃, R₁₄, R₁₈, R₂₀, R₂₃, R₂₄, R₂₇ and R₂₈ are each independently        H or a C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl,        cycloheteroalkyl, aryl or heteroaryl group each optionally        substituted;    -   R₁₅ and R₁₆ are each independently H or an optionally        substituted C₁-C₆alkyl group; and

R₁₇, R₁₉, R₂₁, R₂₂, R₂₅ and R₂₆ are each independently H or anoptionally substituted C₁-C₄alkyl group or R₂₁ and R₂₂ may be takentogether with the atom to which they are attached to form a 5- to7-membered ring optionally containing another heteroatom selected fromO, N or S; or

the stereoisomers thereof, the tautomers thereof or the pharmaceuticallyacceptable salts thereof.

Solid carriers suitable for use in the composition of the inventioninclude one or more substances which may also act as flavoring agents,lubricants, solubilizers, suspending agents, fillers, glidants,compression aides, binders, tablet-disintegrating agents orencapsulating materials. In powders, the carrier may be a finely dividedsolid which is in admixture with a finely divided compound of formula I.In tablets, the formula I compound may be mixed with a carrier havingthe necessary compression properties in suitable proportions andcompacted in the shape and size desired. Said powders and tablets maycontain up to 99% by weight of the formula I compound. Solid carrierssuitable for use in the composition of the invention include calciumphosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch,gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose,polyvinylpyrrolidine, low melting waxes and ion exchange resins.

Any pharmaceutically acceptable liquid carrier suitable for preparingsolutions, suspensions, emulsions, syrups and elixirs may be employed inthe composition of the invention. Compounds of formula I may bedissolved or suspended in a pharmaceutically acceptable liquid carriersuch as water, an organic solvent, or a pharmaceutically acceptable oilor fat, or a mixture thereof. Said liquid composition may contain othersuitable pharmaceutical additives such as solubilizers, emulsifiers,buffers, preservatives, sweeteners, flavoring agents, suspending agents,thickening agents, coloring agents, viscosity regulators, stabilizers,osmo-regulators, or the like. Examples of liquid carriers suitable fororal and parenteral administration include water (particularlycontaining additives as above, e.g., cellulose derivatives, preferablysodium carboxymethyl cellulose solution), alcohols (including monohydricalcohols and polyhydric alcohols, e.g., glycols) or their derivatives,or oils (e.g., fractionated coconut oil and arachis oil). For parenteraladministration the carrier may also be an oily ester such as ethyloleate or isopropyl myristate.

Compositions of the invention which are sterile solutions or suspensionsare suitable for intramuscular, intraperitoneal or subcutaneousinjection. Sterile solutions may also be administered intravenously.Inventive compositions suitable for oral administration may be in eitherliquid or solid composition form.

For a more clear understanding, and in order to illustrate the inventionmore clearly, specific examples thereof are set forth hereinbelow. Thefollowing examples are merely illustrative and are not to be understoodas limiting the scope and underlying principles of the invention in anyway.

Unless otherwise stated, all parts are parts by weight. The term HPLCdesignates high performance liquid chromatography. The terms THF andDMSO designate tetrahydrofuran and dimethylsulfoxide, respectively.

EXAMPLE 1

Preparation of 1-[(4-methylphenyl)sulfonyl]-1H-indole-3-carboxaldehyde1,4,5,6-tetrahydropyrimidin-2-ylhydrazone

A stirred suspension of1-[(4-methylphenyl)sulfonyl]indole-3-carboxaldehyde (74.8 mg, 0.25 mmol)in isopropanol is treated with 2-hydrazine-1,4,5,6-tetrahydropyrimidinehydrobromide (60.5 mg, 0.25 mmol) and concentrated HCl (5 μL), heated at80° C. for 2 h, cooled to room temperature and concentrated in vacuo.The resultant residue is purified by HPLC to give the title product,53.2 mg (42% yield), identified by HPLC¹ and mass spectral analyses.

¹HPLC conditions: Hewlett Packard 1100; YMC ODS-A 4.6 mm×50 mm 5 ucolumn at 23° C.; 10 uL injection; Solvent A: 0.05% TFA/water; SolventB: 0.05% TFA/acetonitrile; Gradient: Time 0: 98% A; 1 min: 98% A; 7 min:10% A, 8 min: 10% A; 8.9 min: 98% A; Post time 1 min. Flow rate 2.5mL/min; Detection: 220 and 254 nm DAD.

EXAMPLE 2

Preparation of2-{Cyclohexyl[1-(phenylsulfonyl)-1H-indol-3-yl]methylidene}-hydrazinecarboximidamide

A solution of indole (11.7 g, 0.1 mol) in THF is added to a stirredmixture of NaH (60% dispersion in mineral oil, 4.2, g 0.105 mol), DMSOand THF. The reaction mixture is stirred for 1 h at room temperature,cooled to 0° C., treated with phenylsulfonyl chloride (13.3 mL, 0.15mol), stirred at ambient temperatures for 3 h, quenched with water andextracted with ethyl acetate. The extracts are combined, dried overMgSO₄ and concentrated in vacuo. The resultant residue is crystallizedin ethanol and filtered. The filtercake is air-dried to give1-phenylsulfonylindole. A portion of this 1-phenylsulfonylindole (257mg, 1.0 mmol) and cyclohexylcarbonyl chloride (0.175 mL, 1.3 mmol) inmethylene chloride is treated with tin tetrachloride (97 μL, 1.9 mmol)at room temperature, shaken for 6 h, quenched with saturated NaHCO₃ andextracted with ethylacetate. The extracts are combined and concentratedin vacuo to give a residue. The residue is suspended in isopropanol,treated sequentially with concentrated HCl (50 μL) and aminoguanidinebicarbonate (100 mg, 0.5 mmol), heated at 80° C. for 4 h, cooled to roomtemperature and concentrated in vacuo. The resultant residue is purifiedby HPLC to afford the title product 37.7 mg (17% yield), identified byHPLC¹ and mass spectral analyses.

¹HPLC conditions: Hewlett Packard 1100; YMC ODS-A 4.6 mm×50 mm 5 ucolumn at 23° C.; 10 uL injection; Solvent A: 0.05% TFA/water; SolventB: 0.05% TFA/acetonitrile; Gradient: Time 0: 98% A; 1 min: 98% A; 7 min:10% A, 8 min: 10% A; 8.9 min: 98% A; Post time 1 min. Flow rate 2.5mL/min; Detection: 220 and 254 nm DAD.

EXAMPLES 3-9

Preparation of 2-[1-(Arylsulfonyl)indol-3-y]carboxaldehyde hydrazone orHydrazinecarboximidamide Derivatives

Using essentially the same procedures described in Examples 1 and 2 andsubstituting the appropriate arylsulfonyl chloride and aminoguanidine,the compounds shown on Table I are obtained and identified by HPLC andmass spectral analyses. HPLC conditions are the same as that used inExamples 1 and 2.

TABLE I

EX Time NO R5 R6 R7 R8 R10 M + H Min 3 H H H H 4-methylphenyl 356 4.42 4—CH₂—CH₂— CH₃ H 4-methylphenyl 396 4.52 5 H H H isopropyl phenyl 384 4.56 H H H benzyl phenyl 432 4.6 7 H H H isobutyl phenyl 398 4.6 8 H H H2-chlorocinnamyl phenyl 478 5.2 9 H H H methyl phenyl 356 4.2

EXAMPLE 10

Preparation of2{1-[5-Chloro-2-methyl-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboxamidamide

A mixture of 5-chloro-2-methylindole (248 mg, 0.5 mmol) and acetylchloride (0.045 mL, 0.6 mmol) in methylene chloride is treated with a1.0 M solution of tin tetrachloride in methylene chloride (0.55 μL, 0.55mmol), shaken at room temperature for 6 h, quenched with saturatedNaHCO₃ and extracted with ethyl acetate. The extracts are combined andconcentrated in vacuo. The resultant residue and phenylsulfonyl chloride(0.095 mL, 0.75 mmol) are dissolved in THF, treated with NaH (60 mg, 1.5mmol) at room temperature, shaken for 6 h, quenched with saturatedNaHCO₃ and extracted with ethyl acetate. The extracts are combined andconcentrated in vacuo to give a residue. This residue is suspended inisopropanol, treated sequentially with aminoguanidine bicarbonate (100mg, 0.5 mmol) and concentrated HCl (50 μL), heated at 80° C. for 4 h,cooled to room temperature and concentrated in vacuo. This resultantresidue is purified by HPLC to afford the title product, 10 mg (5%yield), identified by HPLC and mass spectral analyses, (M+H) 404;retention time 4.72 min.

EXAMPLES 11-122

Preparation of {[1-(Substituted-sulfonyl) indol-3-yl]alkylidene}hydrazinecarboximidamide derivatives

Using essentially the same procedures described in Examples 1, 2 and 10and employing the appropriately substituted indole substrate, aryl oralkyl sulfonyl chloride and acyl halide, the compounds shown in Table IIare obtained and identified by HPLC and mass spectral analyses. The HPLCconditions used are the same as that described for Example 1.

TABLE II

EX Time NO R1 R2 R8 R9 R10 M + H Min 11 H H CH₃ 4-fluorophenyl phenyl450 5.07 12 H H CH₃ 3-chloro-4- phenyl 483 4.99 fluorophenyl 13 H H CH₃3,4-difluoro- phenyl 468 5.94 phenyl 14 H H CH₃ 2-naphthyl phenyl 4825.75 15 H H CH₃ Phenyl phenyl 432 4.95 16 H CN CH₃ H phenyl 381 4.30 17H I CH₃ H phenyl 481 4.75 18 H NO₂ CH₃ H phenyl 401 4.42 19 H F CH₃ Hphenyl 374 4.42 20 H OCH₃ CH₃ H phenyl 372 4.39 21 H OCH₂C₆H₅ CH₃ Hphenyl 448 5.05 22 H H CH₃ H 2-amino-4-methly-1,3-thiazol-5-yl 392 3.9623 H H CH₃ H 4-aminophenyl 371 4.10 24 H H CH₃ H2,1,3-benzothiodiazol-4-yl 414 4.28 25 H H CH₃ H2,1,3-benzoxadiazol-4-yl 398 4.28 26 H H CH₃ H 4-biphenyl 432 5.02 27 HH CH₃ H 4-bromo-2,5-dichlorothien-3-yl 510 4.91 28 H H CH₃ H4-bromo-5-chlorothien-2-yl 474 5.01 29 H H CH₃ H3-bromo-5-chlorothien-2-yl 474 5.00 30 H H CH₃ H 4-bromophenyl 434 4.6431 H H CH₃ H 2-bromophenyl 434 4.41 32 H H CH₃ H 3-bromophenyl 434 4.6333 H H CH₃ H 5-bromothien-2-yl 440 4.66 34 H H CH₃ H5-chloro-2-methoxyphenyl 420 4.65 35 H H CH₃ H5-chloro-3-methyl-1-benzothien- 460 5.23 2-yl 36 H H CH₃ H6-chloroimidazo[2,1-b][1,3]- 436 4.32 thiazol-5-yl 37 H H CH₃ H5-chlorothien-2-yl 396 4.63 38 H H CH₃ H 5-dimethylamino-1-naphthyl 4494.78 39 H H CH₃ H 4,5-dibromothien-2-yl 519 4.65 40 H H CH₃ H2,5-dichorophenyl 425 4.73 41 H H CH₃ H 2,5-dichlorothien-3-yl 431 4.7642 H H CH₃ H 2,3-dichlorothien-5-yl 431 4.93 43 H H CH₃ H3,5-dimethylisoxazol-4-yl 375 4.26 44 H H CH₃ H 4-fluorophenyl 374 4.4245 H H CH₃ H 5-[1-methyl-5-(trifluoromethyl)- 510 5.001H-pyrazol-3-yl]thien-2-yl 46 H H CH₃ H 2-methyl-5-nitrophenyl 415 4.5647 H H CH₃ H 1-methylimidazol-4-yl 360 3.56 48 H H CH₃ H4-(methylsulfonyl)phenyl 434 4.08 49 H H CH₃ H5-[2-(methylthio)pyrimidin-4- 486 4.89 yl]thien-2-yl 50 H H CH₃ H1-naphthyl 406 4.68 51 H H CH₃ H 2-nitrophenyl 401 4.36 52 H H CH₃ H4-nitrophenyl 401 4.45 53 H H CH₃ H 5-pyridin-2-ylthien-2-yl 439 4.68 54H H CH₃ H 4-(trifluoromethoxy)phenyl 440 4.82 55 H H CH₃ H methyl 2943.78 56 H H n-C₄H₉ H methyl 336 4.16 57 H H Cyclopropyl H methyl 3203.69 58 H H CH₃ H n-butyl 336 4.74 59 H H n-C₄H₉ H n-butyl 378 5.34 60 HH Cyclopropyl H n-butyl 362 4.85 61 H H CH₃ H 4-methoxyphenyl 386 4.8262 H H n-C₄H₉ H 4-methoxyphenyl 428 5.47 63 H H Cyclopropyl H4-methoxyphenyl 412 4.99 64 H H CH₃ H 2-naphthyl 406 4.92 65 H H n-C₄H₉H 2-naphthyl 448 5.72 66 H H Cyclopropyl H 2-naphthyl 432 5.56 67 H Hn-C₄H₉ H phenyl 398 4.78 68 H H Cyclopropyl H phenyl 382 4.57 69 H H CH₃H 3,4-dimethoxyphenyl 416 4.39 70 H H n-C₄H₉ H 3,4-dimethoxyphenyl 4585.02 71 H H Cyclopropyl H 3,4-dimethoxyphenyl 442 4.96 72 H Cl CH₃ Hmethyl 328 3.92 73 H Cl n-C₄H₉ H methyl 370 4.50 74 H Cl Cyclopropyl Hmethyl 354 4.73 75 H Cl CH₃ H butyl 370 5.02 76 H Cl n-C₄H₉ H butyl 4125.78 77 H Cl Cyclopropyl H butyl 396 5.34 78 H Cl CH₃ H 4-methoxyphenyl420 5.17 79 H Cl n-C₄H₉ H 4-methoxyphenyl 462 5.72 80 H Cl Cyclopropyl H4-methoxyphenyl 446 5.39 81 H Cl CH₃ H 2-naphthyl 440 5.30 82 H Cln-C₄H₉ H 2-naphthyl 483 5.83 83 H Cl Cyclopropyl H 2-naphthyl 466 5.5684 H Cl CH₃ H phenyl 390 4.53 85 H Cl n-C₄H₉ H phenyl 432 5.08 86 H ClCyclopropyl H phenyl 416 4.66 87 H Cl CH₃ H 3,4-dimethoxyphenyl 450 5.2188 H Cl n-C₄H₉ H 3,4-dimethoxyphenyl 493 5.32 89 H Cl Cyclopropyl H3,4-dimethoxyphenyl 476 5.02 90 H H CH₃ 4-chlorophenyl methyl 404 4.9291 H H n-C₄H₉ 4-chlorophenyl methyl 446 5.41 92 H H Cyclopropyl4-chlorophenyl methyl 430 4.63 93 H H Cyclopropyl 4-chlorophenyl4-methoxyphenyl 523 5.71 94 H H Cyclopropyl 4-chlorophenyl 2-naphthyl543 5.86 95 H H CH₃ 4-chlorophenyl phenyl 466 4.90 96 H H n-C₄H₉4-chlorophenyl phenyl 509 5.56 97 H H Cyclopropyl 4-chlorophenyl phenyl493 5.27 98 H H CH₃ 4-chlorophenyl 3,4-dimethoxyphenyl 527 5.37 99 H HCyclopropyl 4-chlorophenyl 3,4-dimethoxyphenyl 553 5.56 100 F H CH₃ Hmethyl 312 3.94 101 F H n-C₄H₉ H methyl 354 4.4  102 F H Cyclopropyl Hmethyl 338 4.15 103 F H CH₃ H n-butyl 354 4.86 104 F H n-C₄H₉ H n-butyl396 5.62 105 F H Cyclopropyl H n-butyl 380 5.17 106 F H CH₃ H4-methoxyphenyl 404 5.02 107 F H n-C₄H₉ H 4-methoxyphenyl 446 5.12 108 FH Cyclopropyl H 4-methoxyphenyl 430 4.76 109 F H CH₃ H 2-naphthyl 4245.32 110 F H n-C₄H₉ H 2-naphthyl 466 5.34 111 F H Cyclopropyl H2-naphthyl 450 4.80 112 F H CH₃ H phenyl 374 4.45 113 F H n-C₄H₉ Hphenyl 416 5.34 114 F H Cyclopropyl H phenyl 400 4.61 115 F H CH₃ H3,4-dimethoxyphenyl 434 4.97 116 F H n-C₄H₉ H 3,4-dimethoxyphenyl 4765.64 117 F H Cyclopropyl H 3,4-dimethoxyphenyl 460 4.76 118 H F C₂H₅ Hphenyl 388 — 119 H F C₂H₅ H 4-aminophenyl 403 — 120 H F C₂H₅ H2-naphthyl 438 — 121 H Cl C₂H₅ H 4-aminophenyl 419 — 122 H Cl C₂H₅ H2-naphthyl 454 —

EXAMPLE 123

Preparation ofN-Pentyl-2-{1-[1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}-hydrazinecarboximidamide

A solution of thiosemicarbazide (2.73 g, 30 mmol) in ethanol is treatedwith methyl iodate (1.96 mL, 31.5 mmol), heated at 60° C. for 1 h,cooled to room temperature, stored at −20° C. for 18 h and filtered. Thefiltercake is washed with cold ethanol and dried in vacuo. Thethus-obtained S-methylisothiosemicarbazide hydrogen iodide (46.6 mg, 0.2mmol) is dissolved in methanol, treated with pentylamine (24 μL, 0.22mmol), heated at 60° C. for 2 h, cooled to room temperature andconcentrated in vacuo. The resultant residue, 4-pentylaminoguanidinehydrogen iodide (0.2 mmol), is suspended in isopropanol, added to asuspension of 3-acetyl-N-(phenylsulfonyl) indole (59 mg, 0.2 mmol) inisopropanol and concentrated HCl (50 μL), heated at 80° C. for 4 h,cooled to room temperature and concentrated in vacuo to give a residue.This residue is purified by HPLC to give the title product, 17.9 mg (21%yield), identified by HPLC and mass spectral analyses, (M+H) 426;retention time 4.75 min.

EXAMPLES 124-127

Preparation ofN-Substituted-2-{1-[(phenylsulfonyl)-1H-indole-3-yl]ethylidene}hydrazinecarboximidamide

Using essentially the same procedure as described in Example 123 andemploying the appropriate amine, the compounds shown in Table III areobtained and identified by HPLC and mass spectral analyses. The HPLCconditions are the same as that used for Example 1.

TABLE III

Ex Time No. R6 M + H Min. 124 n-propyl 398 5.08 125 benzyl 446 4.91 126Pyridin-2-ylmethyl 447 4.54 127 2-hydroxyethyl 400 4.23

EXAMPLES 128-130

Preparation of2[1-(1-Substituted-1H-indol-3-yl)ethylidene]hydrazinecarboximidamide

Using essentially the same procedure described in Example 10 andemploying phenyl chloroformate, phenyl isocyanate or benzoyl chloride inplace of ClSO₂R₁₀, the compounds shown in Table IV are obtained andidentified by HPLC and mass spectral analyses.

TABLE IV

Ex Time No. Q R10 M + H Min. 128 CO₂ phenyl 336 4.52 129 CONH phenyl 3354.39 130 CO phenyl 320 3.32

EXAMPLE 131

Preparation of Cyclohexane-1,3-dione mono-(4-chlorophenyl)hydrazone

A solution of 1,3-cyclohexanedione (5.05 g, 45 mmol) in water is treatedover a 10 min period with an aqueous suspension ofp-chlorophenylhydrazine (8.06 g, 45 mmol), stirred at room temperaturefor 16 h and filtered. The filtercake is washed with water and dried invacuo to give the title product which is used as in Example 132.

EXAMPLE 132

Preparation of 6-Chloro-4-oxo-1,2,3,4-tetrahydrocarbazole

A mixture of cyclohexane-1,3-dione mono-(4-chlorophenyl) hydrazone (45mmol) obtained in Example 131 and trifluoroacetic acid (30 mL) is heatedto 80° C. for 16 h, cooled to room temperature, poured over ice waterand filtered. The filtercake is dried and recrystallized fromethanol/water to afford the title product, 4.2 g (42% yield), identifiedby HPLC and mass spectral analyses.

EXAMPLE 133

Preparation of6-chloro-1-(phenylsulfonyl)-4-oxo-1,2,3,4-tetrahydrocarbazole

A solution of 6-chloro-4-oxo-1,2,3,4-tetrahydrocarbazole (109 mg, 0.5mmol) in THF is treated with NaH (60 mg, 60% dispersion in mineral oil,1.5 mmol), stirred for 30 min., treated with phenylsulfonyl chloride(132 mg, 0.5 mmol), shaken for 8 h and concentrated in vacuo. Theresultant residue is dissolved in ethyl acetate, washed with water andreconcentrated in vacuo to afford the title product which is used as isin Example 134.

EXAMPLE 134

Preparation of2-[6-Chloro-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]hydrazinecarboximidamide

A suspension of6-chloro-1-(phenylsulfonyl)-4-oxo-1,2,3,4-tetrahydrocarbazole (0.5 mmol)obtained in Example 133 in isopropanol and concentrated HCl (50 μL) istreated with aminoguanidine bicarbonate (66 mg, 0.5 mmol), heated at 80°C. for 4 h, cooled to room temperature and concentrated in vacuo. Theresultant residue is purified by HPLC to afford the title product, 15.8mg (7% yield), identified by HPLC and mass spectral analyses, (M+H) 416;retention time 4.49 min.

EXAMPLES 135-142

Preparation of2-[6-Substituted-9-(arylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]hydrazinecarboximidamide derivatives

Using essentially the same procedures described in Examples 132 to 134and employing the appropriate arylsulfonyl chloride and aminoguanidinederivative, the compounds shown in Table V are obtained and identifiedby HPLC and mass spectral analyses.

TABLE V

EX Time NO R2 R5 R6 R10 M + H Min 135 H H H phenyl 382 4.48 136 Br H Hphenyl -0- 4.80 137 Cl H H methyl 354 4.54 138 Cl H H 4-methoxyphenyl446 4.59 139 Cl H H 2-naphthyl 466 4.78 140 Cl H H 3,4-dimethoxyphenyl476 4.59 141 H —CH₂—CH₂— phenyl — — 142 Cl —CH₂—CH₂— phenyl — —

EXAMPLE 143

Comparative Evaluation of 5-HT6 Binding Affinity of Test Compounds

The affinity of test compounds for the serotonin 5-HT6 receptor isevaluated in the following manner. Cultured Hela cells expressing humancloned 5-HT6 receptors are harvested and centrifuged at low speed(1,000×g) for 10.0 min to remove the culture media. The harvested cellsare suspended in half volume of fresh physiological phosphate bufferedsaline solution and recentrifuged at the same speed. This operation isrepeated. The collected cells are then homogenized in ten volumes of 50mM Tris.HCl (pH 7.4) and 0.5 mM EDTA. The homogenate is centrifuged at40,000×g for 30.0 min and the precipitate is collected. The obtainedpellet is resuspended in 10 volumes of Tris.HCl buffer and recentrifugedat the same speed. The final pellet is suspended in a small volume ofTris.HCl buffer and the tissue protein content is determined in aliquotsof 10-25 μl volumes. Bovine Serum Albumin is used as the standard in theprotein determination according to the method described in Lowry et al.,J. Biol. Chem., 193:265 (1951). The volume of the suspended cellmembranes is adjusted to give a tissue protein concentration of 1.0mg/ml of suspension. The prepared membrane suspension (10 timesconcentrated) is aliquoted in 1.0 ml volumes and stored at −70° C. untilused in subsequent binding experiments.

Binding experiments are performed in a 96 well microtiter plate format,in a total volume of 200 μl. To each well is added the followingmixture: 80.0 μl of incubation buffer made in 50 mM Tris.HCl buffer (pH7.4) containing 10.0 mM MgCl₂ and 0.5 mM EDTA and 20 μl of [³H]-LSD(S.A., 86.0 Ci/mmol, available from Amersham Life Science), 3.0 nM. Thedissociation constant, K_(D) of the [³H]LSD at the human serotonin 5-HT6receptor is 2.9 nM, as determined by saturation binding with increasingconcentrations of [³H]LSD. The reaction is initiated by the finaladdition of 100.0 μl of tissue suspension. Nonspecific binding ismeasured in the presence of 10.0 μM methiothepin. The test compounds areadded in 20.0 μl volume.

The reaction is allowed to proceed in the dark for 120 min at roomtemperature, at which time, the bound ligand-receptor complex isfiltered off on a 96 well unifilter with a Packard Filtermate® 196Harvester. The bound complex caught on the filter disk is allowed to airdry and the radioactivity is measured in a Packard TopCount® equippedwith six photomultiplier detectors, after the addition of 40.0 μlMicroscint®-20 scintillant to each shallow well. The unifilter plate isheat-sealed and counted in a PackardTopCount® with a tritium efficiencyof 31.0%.

Specific binding to the 5-HT6 receptor is defined as the totalradioactivity bound less the amount bound in the presence of 10.0 μMunlabeled methiothepin. Binding in the presence of varyingconcentrations of test compound is expressed as a percentage of specificbinding in the absence of test compound. The results are plotted aslogit % bound versus log concentration of test compound. Nonlinearregression analysis of data points with a computer assisted programPrism® yields both the IC₅₀ and the K_(i) values of test compounds with95% confidence limits.

The amount of displacement by the test compound is given in percent (%)inhibition and is derived from the following equation:${\%\quad{inhibition}} = {\left( {1 - \frac{B_{0} - {NSB}}{{TB} - {NSB}}} \right)100}$where B₀ is the amount of CPM bound in the presence of the testingagent. NSB represents the CPM bound in the presence of a saturatingconcentration of a displacer and TB represents the total amount of CPMbound at zero (0) concentration of test compound.

Alternatively, a linear regression line of decline of data points isplotted, from which the IC₅₀ value can be read off and the K_(i) valuedetermined by solving the following equation:$K_{i} = \frac{{IC}_{50}}{1 + {L/K_{D}}}$where L is the concentration of the radioactive ligand used and K_(D) isthe dissociation constant of the ligand for the receptor, both expressedin nM. Using this assay, the % inhibition and K_(i) values shown inTable VI are obtained.

TABLE VI Test Compound Dose 5-HT6 Binding Ki (Ex. No.) (nM) % Inhibition(nM) — 1 1000 56.0 — 2 1000 69.2 — 3 1000 71.0 — 4 1000 71.9 — 5 100091.5 — 6 1000 97.8 11 7 1000 98.5 12 8 1000 95.2 — 9 1000 99.5  7 121000 75.6 — 13 1000 86.0 — 14 1000 85.4 — 15 100 67.1 — 16 10 40.6 — 1710 52.0 — 18 100 77.9 — 19 100 82.4 — 20 100 76.3 — 21 1000 57.4 — 22100 90.5  8 23 100 92.9  2 24 100 62.9 — 25 100 79.6 15 26 100 39.7 — 27100 33.8 — 28 100 58.3 — 29 100 60.3 — 30 100 65.0 — 31 100 83.3 13 32100 76.2 26 33 100 76.4 19 34 100 48.0 — 35 100 39.1 — 36 100 86.4  8 37100 75.2 25 38 100 25.8 — 39 100 62.1 — 40 100 33.3 — 41 100 55.0 — 42100 46.3 — 43 100 68.9 — 44 100 75.5 33 45 100 23.5 — 46 100 41.0 — 47100 81.1 46 48 100 43.9 — 49 100 33.0 — 50 100 63.5 — 51 100 70.1 — 52100 28.2 — 53 100 38.4 — 54 100 26.2 — 55 100 68.2 — 56 1000 76.9 — 57100 40.4 — 58 100 78.3 — 59 1000 77.7 — 60 100 62.6 — 61 1000 83.6 — 621000 68.3 — 63 100 58.9 — 64 1000 89.6 — 65 1000 62.3 — 66 10 35.1 — 67100 66.3 — 68 10 68.3 — 69 100 72.4 12 70 1000 89.8 — 71 100 61.5 — 72100 75.1 — 73 1000 71.0 — 74 100 68.5 — 75 100 84.6 — 76 1000 74.5 — 7710 44.3 — 78 1000 85.5 — 79 1000 61.0 — 80 100 74.0 — 82 1000 46.9 — 831000 89.3 — 84 100 81.7 — 85 100 57.5 — 86 100 78.1 — 87 1000 88.9 — 881000 65.6 — 89 100 71.9 — 90 1000 63.5 — 91 1000 9.0 — 94 1000 27.9 — 951000 89.6 — 96 1000 20.0 — 98 1000 53.3 — 100 100 83.8 18 101 1000 77.4— 102 10 41.1 — 103 100 69.4 — 104 1000 81.3 — 105 100 58.4 — 106 100064.4 — 107 1000 61.5 — 109 1000 67.8 — 110 1000 60.2 — 111 100 27.6 —112 1000 94.6 — 114 100 85.2 — 115 1000 89.2 — 116 1000 73.5 — 117 10078.2 — 118 — —  7 119 — —  2 120 — — 85 121 — —  9 122 — — 101  123 10034.0 12 124 100 75.2 — 125 100 39.1 — 126 100 37.7 — 127 100 83.3 — 128100 23.9 — 129 100 23.4 — 130 100 49.6 —

1. A compound of formula I

wherein X is N or CR₃; Y is N or CR₄; Q is SO₂, CO, CO₂, CONR or CSNR₁₂;R₁, R₂, R₃ and R₄ are each independently H, halogen, CN, OCO₂R₁₃, CO₂R₁₄, CONR₁₅R₁₆, NR₁₇SO₂R₁₈, NR₁₉COR₂₈, SO_(n)R₂₀, NR₂₁R₂₂, OR₂₃, COR₂₄or a C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl,cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;R₅, R₆ and R₇ are each independently H or a C₁-C₆alkyl, C₂-C₆alkenyl,C₂-C₆alkynyl, C₃-C₁₂cycloalkyl, cycloheteroalkyl, aryl or heteroarylgroup each optionally substituted or R₅ and R₆ maybe taken together withthe atoms to which they are attached to form an optionally substituted5- to 7-membered ring; R₈ is H or a C₁-C₆alkyl or C₃-C₁₀cycloalkyl groupeach optionally substituted; R₉ is H, halogen, CN, NO₂, NR₂₅R₂₆, OR₂₇ ora C₁-C₆alkyl, aryl or heteroaryl group each optionally substituted or R₈and R₉ may be taken together with the atoms to which they are attachedto form an optionally substituted 5- to 7-membered ring optionallycontaining one or two heteroatoms selected from O, N or S; R₁₀ is aC₁-C₆alkyl, aryl or heteroaryl group each optionally substituted or anoptionally substituted 8- to 13-membered bicyclic or tricyclic ringsystem having a N atom at the bridgehead and optionally containing 1, 2or 3 additional heteroatoms selected from N, O or S with the provisothat when R₈ is H or C₁-C₆alkyl and Q is CO then R₁₀ must be other thanC₁-C₆alkyl or aryl; n is 0 or an integer of 1 or 2; R₁₁ and R₁₂ are eachindependently H or a C₁-C₆alkyl, aryl or heteroaryl group eachoptionally substituted; R₁₃, R₁₄, R₁₈, R₂₀, R₂₃, R₂₄, R₂₇ and R₂₈ areeach independently H or a C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,C₃-C₆cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group eachoptionally substituted; R₁₅ and R₁₆ are each independently H or anoptionally substituted C₁-C₆alkyl group; and R₁₇, R₁₉, R₂₁, R₂₂, R₂₅ andR₂₆ are each independently H or an optionally substituted C₁-C₄alkylgroup or R₂₁ and R₂₂ may be taken together with the atom to which theyare attached to form a 5- to 7-membered ring optionally containinganother heteroatom selected from O, N or S; or the stereoisomersthereof, the tautomers thereof or the pharmaceutically acceptable saltsthereof.
 2. The compound according to claim 1 wherein Q is SO₂.
 3. Thecompound according to claim 1 wherein R₁₀ is an aryl or heteroaryl groupeach optionally substituted or an optionally substituted 8- to13-membered bicyclic or tricyclic ring system having a N atom at thebridgehead and optionally containing 1, 2 or 3 additional heteroatomsselected from N, O or S.
 4. The compound according to claim 1 wherein Xis CR₃ and Y is CR₄.
 5. The compound according to claim 2 wherein R₉ isH.
 6. The compound according to claim 2 wherein X is CR₃; Y is CR₄; andR₉ is H.
 7. The compound according to claim 6 wherein R₁₀ is an aryl orheteroaryl group each optionally substituted or an optionallysubstituted 8- to 13-member bicyclic or tricyclic ring system having a Natom at the bridgehead and optionally containing 1, 2 or 3 additionalheteroatoms selected from N, O or S.
 8. The compound according to claim2 selected from the group consisting of:2-[6-chloro-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]hydrazinecarboximidamide;2-[6-chloro-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one4,5-dihydro-1H-imidazol-2-ylhydrazone;2-[6-chloro-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one4,5-dihydro-1H-imidazol-2-yl(methyl)hydrazone;2-[9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]hydrazinecarboximidamide;2-[6-bromo-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one4,5-dihydro-1H-imidazol-2-ylhydrazone;2-[6-bromo-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one4,5-dihydro-1H-imidazol-2-yl(methyl)hydrazone;2-[6-bromo-9-(phenylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]hydrazinecarboximidamide;2-{6-chloro-9-[(4-methoxyphenyl)sulfonyl]-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene}hydrazinecarboximidamide;2-{9-[(2-amino-4-methyl-1,3-thiazol-5-yl)sulfonyl]-6-chloro-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene}hydrazinecarboximidamide;2-[6-chloro-9-(2-naphthylsulfonyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]-hydrazinecarboximidamide;2-{6-chloro-9-[(3,4-dimethoxyphenyl)sulfonyl]-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene}hydrazinecarboximidamide;2-(9-phenylsulfonyl-2,2,6-trimethyl-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene)-hydrazinecarboximidamide;2-(6-methyl-2-phenyl-9-phenylsulfonyl-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene)hydrazinecarboximidamide;2-(6-methyl-9-phenylsulfonyl-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene)hydrazinecarboximidamide;2-(6-isopropyl-2,2-dimethyl-9-phenylsulfonyl-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene)hydrazinecarboximidamide;2-(6-isopropyl-2-phenyl-9-phenylsulfonyl-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene)hydrazinecarboximidamide;2-[2,2-dimethyl-9-phenylsulfonyl-6-(trifluoromethoxy)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]hydrazinecarboximidamide;2-(6-bromo-2,2-dimethyl-9-phenylsulfonyl-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene)-hydrazinecarboximidamide;2-(6-bromo-2-phenyl-9-phenylsulfonyl-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene)hydrazinecarboximidamide;the stereoisomers thereof; and the pharmaceutically acceptable saltsthereof.
 9. The compound according to claim 6 selected from the groupconsisting of: 1-[(4-methylphenyl)sulfonyl]-1H-indole-3-carboxaldehyde1,4,5,6-tetrahydropyrimidin-2-ylhydrazone;2-({1-[(4-methylphenyl)sulfonyl]-1H-indol-3-yl}methylidene)hydrazinecarboximidamide;1-[(4-methylphenyl)sulfonyl]-1H-indole-3-carboxaldehyde4,5-dihydro-1H-imidazol-2-yl(methyl)hydrazone;2-{cyclohexyl[1-(phenylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide;2-{2-methyl-1-[1-(phenylsulfonyl)-1H-indol-3-yl]propylidene}hydrazinecarboximidamide;2-{2-phenyl-1-[1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{3-methyl-1-[1-(phenylsulfonyl)-1H-indol-3-yl]butylidene}hydrazinecarboximidamide;2-{1-[1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{1-[5-chloro-2-methyl-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{1-[2-(4-fluorophenyl)-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{1-[5-cyano-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{1-[5-iodo-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{1-[5-nitro-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{1-[5-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{[5-methoxy-1-(phenylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide;2-{[5-(benzyloxy)-1-(phenylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide;2-(1-{1-[(2-amino-4-methyl-1,3-thiazol-5-yl)sulfonyl]-1H-indol-3-yl}ethylidene)-hydrazinecarboximidamide;2-(1-{1-[(4-aminophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-{1-[1-(2,1,3-benzothiadiazol-4-ylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{1-[1-(2,1,3-benzoxadiazol-4-ylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{1-[1-([1,1′-biphenyl]-4-ylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-(1-{1-[(4-bromo-2,5-dichlorothien-3-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(4-bromo-5-chlorothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(3-bromo-5-chlorothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(4-bromophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(5-bromothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(5-chloro-2-methoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(5-chlorothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-[1-(1-{[5-(dimethylamino)-1-naphthyl]sulfonyl}-1H-indol-3-yl)ethylidene]hydrazinecarboximidamide;2-(1-{1-[(4,5-dibromothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(2,5-dichlorophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(2,5-dichlorothien-3-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(4,5-dichlorothien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(3,5-dimethylisoxazol-4-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(4-fluorophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-{1-[1-({5-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]thien-2-yl}sulfonyl]-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-(1-{1-[(2-methyl-5-nitrophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(1-methyl-1H-imidazol-4-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-[1-(1-{[4-(methylsulfonyl)phenyl]sulfonyl}-1H-indol-3-yl)ethylidene]hydrazinecarboximidamide;2-{1-[1-({5-[2-(methylthio)pyrimidin-4-yl]thien-2-yl}sulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{1-[1-(1-naphthylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-(1-{1-[(2-nitrophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(4-nitrophenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(5-pyridin-2-ylthien-2-yl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-[1-(1-{[4-(trifluoromethoxy)phenyl]sulfonyl}-1H-indol-3-yl)ethylidene]hydrazinecarboximidamide;2-(1-{1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(1-{1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}pentylidene)hydrazinecarboximidamide;2-(cyclopropyl{1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}methylidene)hydrazinecarboximidamide;2-{1-[1-(2-naphthylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{1-[1-(2-naphthylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide;2-{cyclopropyl[1-(2-naphthylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide;2-{1-[1-(phenylsulfonyl)-1H-indol-3-yl]pentylidene}hydrazinecarboximidamide;2-{cyclopropyl[1-(phenylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide;2-(1-{1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-(cyclopropyl{1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}methylidene)hydrazine-carboximidamide;2-(1-{5-chloro-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)-hydrazinecarboximidamide;2-[{5-chloro-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}(cyclopropyl)methylidene]hydrazinecarboximidamide;2-{1-[5-chloro-1-(2-naphthylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide2-{1-[5-chloro-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-[[5-chloro-1-(phenylsulfonyl)-1H-indol-3-yl](cyclopropyl)methylidene]hydrazinecarboximidamide;2-(1-{5-chloro-1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-[{5-chloro-1-[(3,4-dimethoxyphenyl)sulfonyl]-1H-indol-3-yl}(cyclopropyl)-methylidene]hydrazincarboximidamide;2-(cyclopropyl{6-fluoro-1-[(4-methoxyphenyl)sulfonyl]-1H-indol-3-yl}methylidene)-hydrazinecarboximidamide;2-{1-[6-fluoro-1-(2-naphthylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{1-[6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamide;2-{cyclopropyl[6-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl]methylidene}hydrazinecarboximidamide;2-(1-{1-[(3,4-dimethoxyphenyl)sulfonyl]-6-fluoro-1H-indol-3-yl}ethylidene)hydrazinecarboximidamide;2-{1-[5-fluoro-1-(phenylsulfonyl)-1H-indol-3-yl]propylidene}hydrazinecarboximidamide;2-(1-{1-[(4-aminophenyl)sulfonyl]-5-fluoro-1H-indol-3-yl}propylidene)hydrazinecarboximidamide;2-{1-[5-fluoro-1-(2-naphthylsulfonyl)-1H-indol-3-yl]propylidene}hydrazinecarboximidamide;2-(1-{1-[(4-aminophenyl)sulfonyl]-5-chloro-1H-indol-3-yl}propylidene)hydrazinecarboximidamide;2-{1-[5-chloro-1-(2-naphthylsulfonyl)-1H-indol-3-yl]propylidene}hydrazinecarboximidamide;N-(2-hydroxyethyl)-2-{1-[1-(phenylsulfonyl)-1H-indol-3-yl]ethylidene}hydrazinecarboximidamidethe stereoisomers thereof; and the pharmaceutically acceptable saltsthereof.
 10. A pharmaceutical composition which comprises apharmaceutically acceptable carrier and an effective amount of acompound of formula I

wherein X is N or CR₃; Y is N or CR₄; Q is SO₂, CO, CO₂, CONR or CSNR₁₂;R₁, R₂, R₃ and R₄ are each independently H, halogen, CN, OCO₂R₁₃, CO₂R₁₄, CONR₁₅R₁₆, NR₁₇SO₂R₁₈, NR₁₉COR₂₈, SO_(n)R₂₀, NR₂₁R₂₂, OR₂₃, COR₂₄or a C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl,cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;R₅, R₆ and R₇ are each independently H or a C₁-C₆alkyl, C₂-C₆alkenyl,C₂-C₆alkynyl, C₃-C₁₂cycloalkyl, cycloheteroalkyl, aryl or heteroarylgroup each optionally substituted or R₅ and R₆ maybe taken together withthe atoms to which they are attached to form an optionally substituted5- to 7-membered ring; R₈ is H or a C₁-C₆alkyl or C₃-C₁₀cycloalkyl groupeach optionally substituted; R₉ is H, halogen, CN, NO₂, NR₂₅R₂₆, OR₂₇ ora C₁-C₆alkyl, aryl or heteroaryl group each optionally substituted or R₈and R₉ may be taken together with the atoms to which they are attachedto form an optionally substituted 5- to 7-membered ring optionallycontaining one or two heteroatoms selected from O, N or S; R₁₀ is aC₁-C₆alkyl, aryl or heteroaryl group each optionally substituted or anoptionally substituted 8- to 13-membered bicyclic or tricyclic ringsystem having a N atom at the bridgehead and optionally containing 1, 2or 3 additional heteroatoms selected from N, O or S with the provisothat when R₈ is H or C₁-C₆alkyl and Q is CO then R₁₀ must be other thanC₁-C₆alkyl or aryl; n is 0 or an integer of 1 or 2; R₁₁ and R₁₂ are eachindependently H or a C₁-C₆alkyl, aryl or heteroaryl group eachoptionally substituted; R₁₃, R₁₄, R₁₈, R₂₀, R₂₃, R₂₄, R₂₇ and R₂₈ areeach independently H or a C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,C₃-C₆cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group eachoptionally substituted; R₁₅ and R₁₆ are each independently H or anoptionally substituted C₁-C₆alkyl group; and R₁₇, R₁₉, R₂₁, R₂₂, R₂₅ andR₂₆ are each independently H or an optionally substituted C₁-C₄alkylgroup or R₂₁ and R₂₂ may be taken together with the atom to which theyare attached to form a 5- to 7-membered ring optionally containinganother heteroatom selected from O, N or S; or the stereoisomersthereof, the tautomers thereof or the pharmaceutically acceptable saltsthereof.
 11. The composition according to claim 10 having a formula Icompound wherein Q is SO₂.
 12. The composition according to claim 11having a formula I compound wherein R₁₀ is an aryl or heteroaryl groupeach optionally substituted or an optionally substituted 8- to 13-memberbicyclic or tricyclic ring system having a N atom at the bridgehead andoptionally containing 1, 2 or 3 additional heteroatoms selected from O,N or S.
 13. The composition according to claim 1 having a formula Icompound wherein X is CR₃ and Y is CR₄.
 14. The composition according toclaim 13 having a formula I compound wherein R₉ is H.